A number of studies have shown that retinoic acid (RA) is a very effective growth suppressor of human ovarian carcinoma cells when administered either alone or in combination with other differentiation inducing agents. However, no information exists concerning the mechanism by which RA acts. As a result, it is difficult to design an optimal therapeutic strategy involving RA. Without such an optimal regimen, it is difficult to accurately access the usefulness of this well-established anti-cancer agent for treatment of ovarian carcinoma. In order to solve this problem, we intend to elucidate the precise role of the nuclear retinoic acid receptors in mediating the growth inhibitory response of human ovarian carcinoma cells to retinoic acid (RA). In addition, we wish to identify genes whose transcription is altered by retinoic acid activation of the nuclear retinoic acid receptors and retinoid-X-receptors. Since such genes would most likely play an important role in regulating ovarian carcinoma cell growth, they would represent excellent molecular markers for both diagnosis of ovarian carcinoma as well as indicators of successful systemic therapy. Finally, we plan to use the knowledge obtained about the mechanism of RA growth suppression to conduct a clinical trial to directly test and monitor the efficacy of using retinoids in the treatment of ovarian cancer.